title: Phosphorylation networks regulating JNK activity in diverse genetic backgrounds.
abstract: Cellular signaling networks have evolved to enable swift and accurate responses, even in the face of genetic or environmental perturbation. Thus, genetic screens may not identify all the genes that regulate different biological processes. Moreover, although classical screening approaches have succeeded in providing parts lists of the essential components of signaling networks, they typically do not provide much insight into the hierarchical and functional relations that exist among these components. We describe a high-throughput screen in which we used RNA interference to systematically inhibit two genes simultaneously in 17,724 combinations to identify regulators of Drosophila JUN NH(2)-terminal kinase (JNK). Using both genetic and phosphoproteomics data, we then implemented an integrative network algorithm to construct a JNK phosphorylation network, which provides structural and mechanistic insights into the systems architecture of JNK signaling.
authors.affiliation: Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02215, USA. cbakal@receptor.med.harvard.edu
authors.forename: Chris
authors.initials: C
authors.lastname: Bakal
authors.forename: Rune
authors.initials: R
authors.lastname: Linding
authors.forename: Flora
authors.initials: F
authors.lastname: Llense
authors.forename: Elleard
authors.initials: E
authors.lastname: Heffern
authors.forename: Enrique
authors.initials: E
authors.lastname: Martin-Blanco
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
mesh_terms: D000465:Algorithms; D000818:Animals; D002460:Cell Line; D019295:Computational Biology; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D017344:Genes, Insect; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D053858:Metabolic Networks and Pathways; D010766:Phosphorylation; D040901:Proteomics; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D048031:JNK Mitogen-Activated Protein Kinases